Autologous Stem Cell Transplantation for T-Cell

Lymphomas
Perrone Giulia a and Paolo Corradini a,b

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of T-cell malignancies
characterized by a very poor outcome. The optimal treatment for PTCLs remains controversial. The role
of stem cell transplantation in PTCLs has been investigated; however, no randomized control studies
specifically dedicated to PTCLs are currently available. Several retrospective and prospective studies have
suggested that high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT)
may improve the survival in patients with chemosensitive T-cell lymphoma, either upfront or as salvage
treatment. This review provides a summary of the current literature with the intent to explore the role of
ASCT in various clinical scenarios.
Semin Hematol 51:59–66. C 2014 Elsevier Inc. All rights reserved.

P eripheral T-cell lymphomas (PTCLs) are a hetero-

geneous group of aggressive non-Hodgkin lympho-
mas (NHLs) representing approximately 10%–
15% of lymphoid neoplasms in Western countries.1
Clinical appearance and manifestation sites vary widely
overall higher incidence in Asia and Central/South America
than Western countries. The majority of patients are
diagnosed in advance stage, with widespread disease.2 The
median age at diagnosis is 60 years, with approximately
40% of cases occurring between the ages of 55 and 74, and
among the different subgroups of PTCLs, and the classi- only about 5% occurring after the age of 85. However,
fication by morphology only appears to be extremely several subtypes had a median age that is much younger,
difficult. The integration of morphologic, immunopheno- including ALCL, ALKþ (33 years); hepatosplenic type (34
typic, genetic, and clinical features let to identify four years); and subcutaneous panniculitis-like PTCL (33 years).
subgroups: cutaneous T-cell lymphomas, primary nodal It has been long recognized that the majority of PTCLs
PTCLs, extranodal lymphomas, and leukemic forms. This have a very poor prognosis compared to their B-cell
review will deal with the nodal and extranodal forms. Nodal counterpart.3Treatment outcomes for PTCLs are substan-
PTCLs represent the most common and heterogeneous tially inferior to B-cell lymphoma. T-cell phenotype per se
subtype of PTCL, including angioimmunoblastic T-cell is an independent negative prognostic factor.4 The Interna-
lymphoma (AITL, 18%), anaplastic lymphoma kinase- tional T-Cell Lymphoma Study reported an overall survival
positive (ALKþ, 7%) and anaplastic lymphoma kinase- (OS) and failure-free survival (FFS) of only 10% at 10–15
negative (ALK–, 5%), anaplastic large cell lymphoma years.5 Several prognostic scores have been evaluated to
(ALCL), adult T-cell lymphoma (ATCL, 10%), and not divide patients into low risk or high risk. The International
otherwise specified (NOS, 26%). The extranodal form Prognostic Index (IPI) appears to be prognostic for patients
includes the rare but well-characterized form of T-cell with PTCLs. Other prognostic models have been devel-
lymphoma known as extranodal natural killer (NK)/T-cell oped specifically for patients with PTCLs. The Prognostic
lymphoma, nasal type (nasal NKTCL), as well as enter- Index for PTCLs (PIT score),6 based on age, lactate
opathy type intestinal T-cell lymphoma (ENTL), and dehydrogenase (LDH), performance status, and bone
hepatosplenic T-cell lymphoma (HSL). The epidemiology marrow involvement, stratifies patients into more distinct
of PTCLs shows important geographic variations, with prognostic groups compared to the IPI.7
Regarding the impact of histologic subtypes, the most
a
important prognostic factor is the presence or absence of
Division of Hematology Fondazione IRCCS Istituto Nazionale dei
Tumori, Milano, Italy.
ALK in ALCL.8 The OS of ALKþ ALCL is substantially
b
Department of Hematology, University of Milan, Milano, Italy. better than that seen for ALK- ALCL (70% v 49%,
Conflicts of interest: none. respectively). However, within the good prognostic cat-
Address correspondence to Corradini Paolo, Department of
Hematology and Pediatric Onco-Hematology, Division of Hematol-
egory of ALKþ ALCL, survival was 90% for the low/low
ogy and Stem Cell Transplantation, Fondazione IRCCS Istituto intermediate risk group and 33% for the high/high
Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy. E-mail: intermediate risk group. In multivariate analysis ALK
[Link]@[Link]
expression and IPI were able to predict survival among
0037-1963/$ - see front matter
& 2014 Elsevier Inc. All rights reserved. ALCL patients. Currently, ALK positivity identifies the
[Link] only histologic subtype with good prognosis.

Seminars in Hematology, Vol 51, No 1, January 2014, pp 59–66 59

60 P. Giulia and P. Corradini

Historically, the treatment of PTCL has been largely The discouraging results achieved with conventional
derived from that applied for B-NHL. Anthracycline- therapies let to the investigation of new concepts, includ-
containing chemotherapy regimens were able to induce ing high-dose chemotherapy (HD) followed by autologous
complete remission (CR) in 54% of the patients with stem cell transplantation (ASCT) or allogeneic stem cell
T-cell lymphomas, with an OS of 41%.4 Comparative transplantation (allo-SCT). So far, no randomized control
analysis with B-NHL showed no difference in response trials exclusively dedicated to SCT in PTCL have been
rate; however, T-cell lymphomas relapsed more frequently published; the majority of data derive from retrospective
and earlier than B-cell lymphomas. When the main studies or phase II studies, often including both first-line
subgroups of T-cell lymphoma were analyzed, only ALKþ and relapsed patients, therefore making it extremely
ALCL had an equivalent or even superior prognosis difficult to obtain a conclusive analysis.
compared to aggressive B-NHL.4,8 Here, we review and comment on the role of ASCT in
A retrospective analysis on more than 1,300 newly PTCLs based on the prospective and retrospective data
diagnosed or relapsed/refractory PTCLs, evaluated in the currently available.
International T-Cell Lymphoma Project, reported that the
majority of patients with PTCLs did not clearly benefit
FRONTLINE AUTOLOGOUS STEM CELL
from an anthracycline-containing regimen over a non–
TRANSPLANTATION
anthracycline-containing regimen.2 Moreover, from this
study it emerged that about 30% of PTCLs are primary Randomized trials on frontline ASCT are lacking,
refractory and the survival curve does not reach a plateau, mainly because of the rarity of these diseases; therefore,
with a long-term survival rate of only 10%–30%. Neither no data are currently available to conclusively support the
intensified/escalated chemotherapeutic approaches9,10 nor role of frontline ASCT. However, several phase II pro-
the addition of a monoclonal antibody such as alemtuzu- spective trials have suggested the benefit of upfront ASCT,
mab11 has demonstrated a clear advantage in sustained in particular for patients achieving at least a partial
remission and prolonged survival. In 2010 for the first time response (PR) after induction therapy (Table 1).
the incorporation of etoposide into the CHOP (cyclo- In 2006, the long-term results of two Italian prospec-
phosphamide, doxorubicin, vincristine, prednisone) treat- tive phase II studies on sequential HDT, followed by
ment (CHOEP) was shown to improve event-free survival ASCT, were reported.13 In an-intent-to-treat (ITT) anal-
(EFS), at least in a subset of younger patients with PTCLs, ysis, only 46 of 62 patients (74%) completed the whole
without significant increasing the percentage of adverse program. Progressive disease during the induction phase
events,12 suggesting a novel strategy to investigate further. was the main obstacle for proceeding to the autografting

Table 1. Prospective Studies of Frontline ASCT in PTCL-Exclusive Patients

Status at Transplant Response
Authors PTCLs Transplant Rate TRM Rate PFS OS
D’Amore 166 ORR 82% 72% 1.2% CR/u CR 78% 44% (5 yr) 51% (5 yr)
et al17
PD 16% PR 8%
Reimer 83 CR1 47% 66% 3.6% CR 58% 36% (3 yr) 48% (3 yr)
et al16
PR1 24% PR 8%
Corradini 62 (19 ALKþ) CR1 56% 71% 4.8% CR 89% 30% (12 yr) 34% (12 yr)
et al13
PR1 16% PR11%
PD 24%
Mercadal 41 CR1 49% 41% ND CR 51% 30% (4 yr) 39% (4 yr)
et al15
PR1 10% PR 7%
Rodriguez 26 CR 46% 73% 0% CR 89% 53% (3 yr) 73% (3 yr)
et al14
PR 27% PR 5%
Abbreviations: ASCT, autologous stem cell transplantation; PTCL, peripheral T-cell lymphoma; TRM, transplant-related mortality; PFS,
progression-free survival; OS, overall survival; ALK, alkaline kinase; ORR, overall response rate; CR, complete response; PR, partial
response; PD, disease progression; uCR, unconfirmed CR; ND, not determined.
 Autologous stem cell transplantation for T-cell lymphomas
Table 2. Retrospective Studies on ASCT as Salvage Strategy in PTCL Patients
No. of Median Response Follow-up
First Author Patients Histology Status at Transplant Prior Lines Rate (mo) PFS OS
32
Rodriguez 29 No data CR 38%, PR 48% 3 (1–4) CR 79% 43 32% (3 yr) 39% (3 yr)
Song25 36 PTCL 56%, ALCL 25% CR 42%, PR 50% 2 (1–3) No data 42 37% (3 yr) 48% (3 yr)
Blystad33 40 PTCL 50%, ALCL 35% CR1 27%, PR1 15% No data CR 80% 36 48% (3 yr) 58% (3 yr)
CR2/CR3 43%, PR2
15%
Rodriguez19 115 PTCL 63%, ALCL 22%, CR1 32%, CR2/CR3 No data CR 86% 37 60% (5 yr) 56% (5 yr).
NK/T 15% 24%, PR 38%
Ref. 5% PR 5% CR1 80%, CR2/3
50%, PR 46%
Jantunen30 37 PTCL 38%, ALCL 38%, CR/PR1 49%, CR/ 2 (1-4) CR 76% 24 44% (5 yr) 54% (5 yr)
EATL 14% PR2 38%, Other
13%
PR 5% CR/PR1 64%, CR/PR1 63%,
Other 28% Other 45%
Jagasia34 28 ALCL 54%, PTCL 21%, CR1 3%, CR2 36%, 2 (1-3) No data 36 50% (3 yr) 69% (3 yr)
AITL 11%, NK/T 11% PR1/2 50%, PD
11%
43% (6 yr)
Kewalra- 24 PTCL 58%, ALCL CR 62%, PR 38% No data No data 72 24% (5 yr) 33% (5 yr)
mani26 ALK - 17%, AITL 17%
Kim31 40 PTCL 50%, NK/T 25%, CR 28%, PR 63%, 2 (1-4); CR 60% 16 Median Median 11.5 mo
ALCL 13% PD10% 3.6 mo
PR 10%
PD 20%
Rodriguez20 123 PTCL 57%, ALCL 25%, PR1 36%, CRZ2 2(1-4) CR 37% 61 34% (5 yr) 45% (5 yr)
AITL 8% 36%, PRZ2 16%
PD 9% PR 11%
PD 16%
Smith35 32 PTCL 34%, ALCL 66% CR1/PR1 19%, Ref. 2(1-4) No data 30 18% (5 yr) 34% (5 yr)
26%, Relapse 55%
Chen24 53 PTCL 30%, ALCL 34%, CR1/PR1 28%, CR2/ 2(1-5) No data 60 25% (5 yr) 48% (5 yr)
AITL 17% PR2 49%, PD 19%

61
Table 2 (continued )

62
No. of Median Response Follow-up
First Author Patients Histology Status at Transplant Prior Lines Rate (mo) PFS OS
CR1/PR 51%, CR1/PR 76%,
CR2/PR CR2/PR2 40%,
12%, Ref. Ref. 30%
0%
Yang21 64 PTCL 100% CR1/PR1 5/19%, No data No data 30 44% (3 yr) 53% (3 yr)
CR2/PR2 5/39%,
PD 9.4% CR1/PR1 60%,
PR1 50%,
CR2/PR2 38%,
CR2 71%
Numata22 39 PTCL 19%, ALCL 14%, No data No data CR 59% 78 61% (5 yr) 62% (5 yr) sens/
AITL 17%, NK 11% sens/ref. 68/ ref. 67/38%
29%
Nadema- 67 PTCL 45%, ALCL 45% , CR1/PR1 12%, CR2 No data No data 66 40% (5 yr) 54% (5 yr)
nee36 AITL 10% 31%, PD 30%,
Relapsed 21%
CR1/PR1 CR1/PR1 92%,
75%, Other Other 45%
32%
Abbreviations: ASCT, autologous stem cell transplantation; PTCL, peripheral T-cell lymphoma; PFS, progression-free survival; OS, overall survival; ALCL, anaplastic large cell lymphoma;
NK, natural killer cell; ALK, alkaline kinase; AITL, angioimmunoblastic T-cell lymphoma ; ORR, overall response rate; CR, complete response; PR, partial response; PD, disease progression;
uCR, unconfirmed CR; sens./ref., sensitive/refractory.

P. Giulia and P. Corradini

Autologous stem cell transplantation for T-cell lymphomas 63

phase and the main cause of treatment failure. The high received ASCT, while the remaining did not complete the
progression rate led to disappointing 12-year OS and study due to early progressive disease. In the ITT analysis,
disease-free survival (DFS) curves (34% and 55%, respec- the overall response rate (ORR) after transplant was 66%
tively). However, in multivariate analysis, achieving CR (56% CR and 8% PR). The estimated 3-year OS and PFS
prior to transplant was strongly correlated with a superior for patients in CR were 48% and 36%, respectively. The
10-year EFS compared to less than CR; the 12-years DFS 3-year OS and PFS for the entire population undergoing
of this specific subgroup was projected at 60%, suggesting ASCT was 71%, whereas it was only 11% for those who
that consolidation of CR with ASCT can offer a greater did not undergo transplant. A trend for longer OS was
chance of long-term survival. A separate analysis on ALKþ observed in patients with low/intermediate low IPI
ALCL patients showed the most favorable OS and EFS for (v high/intermediate high) who underwent transplanta-
this specific histology subtype (62% and 54%, respec- tion in CR (v PR). The results of the study suggested that
tively, compared to 21% and 18% for non-ALKþ), with upfront ASCT is an effective treatment in PTCL; how-
a further survival advantage for low-risk age-adjusted IPI ever, pretransplantation treatments need to be improved to
(aaIPI) compared to intermediate–high risk categories. increase both the response and transplantation rate.
In 2007, the GELTAMO experience was reported by Based on the encouraging result reported by the German
Rodriguez, et al.14 Twenty-six patients with nodal PTCL, study on CHOEP treatment,12 the Nordic group designed a
excluding ALKþ ALCL, received three courses of Mega- phase II study17 to evaluate the impact of a dose-intensified
CHOP. Gallium scan–negative patients received one more induction schedule (CHOEP-14 for six cycles) consolidated
course of treatment followed by ASCT, those remaining in first PR/CR with high-dose therapy (BEAM/ASCT).
gallium scan–positive received two courses of salvage After induction, 82% of patients were in CR or PR. Disease
therapy (ifosfamide/etoposide treatment) and, patients refractory to induction treatment was observed in 16% of
with chemosensitive disease proceeded to ASCT. Overall, patients. Among the 70% of patients receiving ASCT, 78%
73% of patients received ASCT and 89% were in CR after were in CR after ASCT, 8% were in PR, and 7%
transplant. After a median follow-up of 3 years, OS and experienced early disease progression. With a median
progression-free survival (PFS) of the entire cohort were follow-up of 60.5 months, 5-year OS and PFS were 51%
73% and 53%, respectively. In the subgroup of patients and 44%, respectively. With respect to prognostic param-
receiving transplant, 2-year OS and PFS were 84% and eters, a significant correlation was observed between IPI
56%, respectively. In univariate analysis, chemosensitive (low/intermediate low v high/intermediate high) and OS.
status after the first three cycles of treatment or at the time In multivariate analysis, ALK- ALCL showed a significantly
of transplant was the only prognostic factor for OS. better outcome as compared with other subtypes. The
Interestingly, to rescue primary resistant or early progres- problem of the assessment of diagnosis by an expert
sive patients, the investigators highlighted the role of pathologist was again raised in this study by the results of
alternative salvage treatment strategy before ASCT. centralized review that modified 13% of original diagnoses.
In 2008 Mercadal, et al,15 on behalf of GELCAB, From the studies reported above, several important
reported the data on 41 PTCL patients, excluding ALKþ points emerge: (1) approximately one third of patients
ALCL and cutaneous forms, treated with intensive chemo- display primary resistant or early progressive disease
therapy (three courses of high-dose CHOP alternating becoming, therefore, not transplant eligible; (2) neverthe-
with three courses of ESHAP [etoposide, methylpredniso- less, among the patients who are able to receive ASCT, the
lone, cytarabine, cisplatin]) followed by ASCT as consol- outcome seems to be superior to conventional chemo-
idation. Only 59% of patients achieved a CR or PR, and therapy; and (3) a treatment strategy including ASCT
an even lower proportion of patients (41%) eventually frontline can lead to long-term response in chemosensitive
received ASCT. The investigators highlighted the high rate patients. The challenge is to make more patients able to
of severe hematologic toxicity and mobilization failure. receive the transplant and this group will be expanded by
After a median follow-up of 3.2 years, 4-year OS and PFS the use of new drugs such as pralatrexete and romidepsine.
were 39% and 30%, respectively. No difference in term of
OS was observed in CR patients who were candidates for
AUTOLOGOUS STEM CELL
ASCT according to whether ASCT was carried out or not.
TRANSPLANTATION IN RELAPSE/
The impact of CHOP regimen before upfront ASCT
REFRACTORY PTCLs
was prospectively evaluated by Reimer, et al.16 From 2000
to 2006, 83 PTCLs (excluding ALKþ ALCL) patients In 1995, the PARMA study18 demonstrated that HDT
were treated with four to six cycles of CHOP followed by followed by ASCT is the treatment of choice for patients
stem cell collection preceded by a mobilizing cycle with relapsed aggressive B-NHL, resulting in 40%–50%
(DexaBEAM [dexamethasone BCNU, etoposide, cytara- long-term DFS; on the contrary, the role of ASCT in
bine, melphalan] or ESHAP). Patients in CR or PR T-cell NHL is less clear and still to be defined. Several
underwent myeloablative chemo-radiotherapy (fractio- retrospective studies have been published on the use of ASCT
nated total-body irradiation and high-dose cyclophospha- as salvage treatment (Table 2). It is important to consider that
mide) followed by ASCT. In this study, 66% of patients the majority of these retrospective studies are heterogeneous
64 P. Giulia and P. Corradini

in terms of histological subgroups, patient characteristics, Clinic, Smith, et al24 evaluated 32 patients with relapsed
prognostic factors, myeloablative regimens, and duration of disease uniformly treated with the same preparative regimens
follow-up. In addition, most of them contain some type of (busulfan/etoposide/cyclophosphamide). Their 5-year OS
bias, largely due to patient selection and inclusion of the and relapse-free survival (RFS) rates were 34% and 18%,
patients receiving either upfront or salvage ASCT. respectively, lower than what has been published in other
The two largest retrospective studies on ASCT in studies. Several publications have retrospectively compared
PTCL were reported by the GELTAMO group. In the outcome of aggressive T- and B-cell lymphoma with
2003, a series of 115 PTCLs patients,19 including ALCL chemosensitive relapsed treated with ASCT. Song, et al25
(22%) and NK/T (15%) subtypes, treated from 1990 to reviewed 36 patients with relapsed or refractory PTCLs
1999 was reported. At the time of transplant 32% of undergoing ASCT and matched them to patients with
patients were in first CR and 24% in second or more CR. aggressive B-NHL treated at the same institution. Patients
With a median follow-up of 37 months, the 5-years OS were similar for age, stage at relapse, presence of extranodal
and DFS were 56% and 60%, respectively. The 5-years disease, and chemosensitivity to salvage treatment. The 3-year
OS rates, according to disease status at transplantation, EFS rates of patients with the PTCLs, ALCL, and diffuse
were 80%, 50%, and 46% for patients in CR1, CR2/ large B-cell lymphoma (DLBCL) were 37%, 67%, and 48%,
CR3, and PR, respectively. In multivariate analysis, only respectively. The 3-year OS rates of patients with the PTCLs,
LDH level before transplantation predicted survival. ALCL, and DLBCL were 37%, 67%, and 48%, respectively.
Patients transplanted in first CR or with low aaIPI had a This study showed inferior outcomes following ASCT in
significantly longer DFS. In 2007, the GELTAMO20 patients with PTCL NOS compared to ALCL and DLBCL.
reported a larger series of 123 patients who received ASCT In 2006 Kewalramani, et al26 evaluated 24 patients under-
as salvage treatment from 1990–2004. The 5-year OS and going ASCT with relapsed or refractory PTCL (ALKþ ALCL
PFS were 45% and 34%, respectively. From multivariate or not documented ALK expression were excluded) who
analysis, three factors emerged as independent factors for responded to first-line or second-line chemotherapy and
outcome: having an aaIPI 41, a high β2-microglobulin compared them with 86 consecutive patients with chemo-
level, or more than one extranodal disease site. Patients sensitive relapsed or primary refractory DLBCL (before the
with no pretransplant adverse factors had an OS and PFS rituximab era). Five-year PFS rates for PTCL and DLBCL
at 5 years of 60% and 43%, respectively. Moreover, PFS were 24% and 34%, respectively (P ¼ .14); the correspond-
and OS of patients in second or subsequent CR at ing OS rates were 33% and 39%, respectively. No significant
transplant (35% and 57%, respectively) were superior differences were found between the two groups with respect
compared to those in second PR (23% and 33%) or with to time to disease progression and survival after progression,
refractory disease (10% and 9%). As in other retrospective but rituximab was not yet available.
studies,21,22 the importance of being in CR at the time of Most of the published data includes heterogeneous
transplant to achieve a long-term survival was emphasized. subtypes of T-cell NHL; however, more recently some
Several studies have specifically described the outcome efforts have been made to define the role of ASCT in
of ASCT in patients with chemosensitive disease. In 2001 specific subtypes. Federico, et al27 retrospectively analyzed
Blystad, et al23 reported a double-institution Scandinavian 243 AITL patients on behalf of the International Periph-
study on 40 patients with chemosensitive disease who eral T-Cell Lymphoma Project. Only 17% of patients
underwent ASCT, either frontline (CR1 27%, PR1 155) were treated with ASCT. Five-year OS was 32% in the
or as salvage treatment (CR2/CR3 43%, PR2 15%) from whole population, confirming the poor outcome of AITL.
1990 over a period of 10 years. With a median follow-up However, no data were specifically reported on the out-
of 36 months, 3-years PFS and OS rates were 48% and come of patients receiving ASCT. A retrospective analysis
58%, respectively. Interestingly, purging of the autograft of the European Bone Marrow Transplant registry
was performed in 13 of the 40 patients; however, no (EBMT)28 on 146 AITL patients demonstrated an OS
conclusive data on its effect on outcome can be acquired. and PFS of 59% and 42% at 4 years. The PFS was higher
With a follow-up of 60 months, Chen, et al24 reported the in patients who received ASCT in CR, achieving 56% at
experience of the Stanford University on 53 PTCL 4 years versus 23% in the case of chemorefractory disease.
patients with chemosensitive disease treated with ASCT Also, extranodal T-cell lymphoma can benefit from
from 1989–2006. The 5-year OS was 76% for patients ASCT. In a prospective observational study, EATL treated
receiving consolidative ASCT in first CR, compared to frontline with alternating courses of IVE (ifosfamide,
48% for patients in second remission or beyond. In vincristine, etoposide) and methotrexate followed by
multivariate analysis, CR status at þ90 days after ASCT ASCT showed a 5-year OS of 60% compared to a
was predictive of longer OS and PFS. In this study, no historical control of 22% with conventional chemother-
benefit was observed with T-cell–purged graft. apy,29 which supports the role of intense upfront regimens
Also, the Japan registry22 demonstrated better long-term as a bridge to transplant. The retrospective study from the
outcome in PTCL patients transplanted in first CR or PR EBMT30 on 44 patients with EATL treated with ASCT
compared to other disease status (5-year OS 72.9% v 45.8%, showed 4-year PFS and OS of 54% and 59%, respectively,
PFS 73.1% v 42.2%). From the database of the Cleveland confirming the possibility of long-term disease control.
Autologous stem cell transplantation for T-cell lymphomas 65

Taken together, these data show that the ASCT as pathology findings and clinical outcomes. J Clin Oncol.
salvage strategy appears feasible and safe with a low 2008;26:4124-30.
morbidity and mortality. Disease status at the time of 3. Vose JM. Peripheral T-cell non-Hodgkin's lymphoma.
Hematol Oncol Clin North Am. 2008;22:997-1005.
transplantation is critical. A better long-term survival in
4. Gisselbrecht C, Gaulard P, Lepage E, et al. Prognostic
patients transplanted in CR is described, compared to
significance of T-cell phenotype in aggressive non-Hodgkin's
patients with other disease status. However, since all data lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte
in this setting are generated retrospectively, the value of (GELA). Blood. 1998;92:76-82.
this observation needs further confirmation. 5. A predictive model for aggressive non-Hodgkin's lymphoma.
The International Non-Hodgkin's Lymphoma Prognostic
Factors Project. N Engl J Med. 1993;329:987-94.
CONCLUSIONS 6. Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell
Across all retrospective and prospective trials that have lymphoma unspecified (PTCL-U): a new prognostic model
addressed the role of ASCT in PTCLs, the procedure was from a retrospective multicentric clinical study. Blood. 2004;
103:2474-9.
considered safe and feasible, but unfortunately resulted in
7. Went P, Agostinelli C, Gallamini A, et al. Marker expression
an unavoidable poor outcome in chemorefractory disease. in peripheral T-cell lymphoma: a proposed clinical-pathologic
The role of frontline ASCT remains to be fully prognostic score. J Clin Oncol. 2006;24:2472-9.
delineated. We currently do not know if achieving CR 8. Falini B, Pileri S, Zinzani PL, et al. ALKþ lymphoma: clinico-
versus PR before transplant, or normalized functional pathological findings and outcome. Blood. 1999;93:2697-706.
imaging, significantly improves long-term outcome. In 9. Mounier N, Simon D, Haioun C, Gaulard P, Gisselbrecht C.
general, patients in CR at transplantation had a better Impact of high-dose chemotherapy on peripheral T-cell
long-term outcome compared with patients achieving less lymphomas. J Clin Oncol. 2002;20:1426-7.
than CR or less than PR.20,21,24,31 In conclusion, all of the 10. Simon A, Peoch M, Casassus P, et al. Upfront VIP-
prospective trials of upfront ASCT demonstrated that reinforced-ABVD (VIP-rABVD) is not superior to CHOP/
chemosensitive disease is the strongest predictor of out- 21 in newly diagnosed peripheral T cell lymphoma. Results
of the randomized phase III trial GOELAMS-LTP95. Br
come; thus, the emerging key message is that only
J Haematol. 2010;151:159-66.
chemosensitive disease seems to benefit from autografting
11. Gallamini A, Zaja F, Patti C, et al. Alemtuzumab (Campath-
and that there is no reason to perform ASCT in refractory 1H) and CHOP chemotherapy as first-line treatment of
patients. In addition, due to the absence of a phase III peripheral T-cell lymphoma: results of a GITIL (Gruppo
trial, we do not know for sure if patients in CR really need Italiano Terapie Innovative nei Linfomi) prospective multi-
consolidation with ASCT. It seems that this is the case if center trial. Blood. 2007;110:2316-23.
we compare the results of conventional chemotherapy 12. Schmitz N, Trumper L, Ziepert M, et al. Treatment and
with ASCT, but this is just speculation. prognosis of mature T-cell and NK-cell lymphoma: an
Early progressive disease (PD) after induction treatment, analysis of patients with T-cell lymphoma treated in studies
which entails about one third of patients, is the major of the German High-Grade Non-Hodgkin Lymphoma
limitation to proceeding with transplant and represents a Study Group. Blood. 2010;116:3418-25.
treatment failure with currently no alternative effective 13. Corradini P, Tarella C, Zallio F, et al. Long-term follow-up
of patients with peripheral T-cell lymphomas treated
strategies. In this context, the use of novel agents may
up-front with high-dose chemotherapy followed by autolo-
potentially improve rate and duration of response and
gous stem cell transplantation. Leukemia. 2006;20:1533-8.
clinical trials are therefore essential, either frontline to 14. Rodriguez J, Conde E, Gutierrez A, et al. Frontline
evaluate if a larger number of patients can retain a chemo- autologous stem cell transplantation in high-risk peripheral
sensitive disease, or in chemorefractory patients before T-cell lymphoma: a prospective study from The Gel-Tamo
transplant to induce a possible response in this subgroup. Study Group. Eur J Haematol. 2007;79:32-8.
In conclusion, regarding the role of SCT, a definitive 15. Mercadal S, Briones J, Xicoy B, et al. Intensive chemo-
statement is still to be defined. Therefore it is strongly therapy (high-dose CHOP/ESHAP regimen) followed by
recommended that patients should be entered into clinical autologous stem-cell transplantation in previously untreated
trials designed to evaluate novel therapeutic strategies. patients with peripheral T-cell lymphoma. Ann Oncol.
2008;19:958-63.
16. Reimer P, Rudiger T, Geissinger E, et al. Autologous stem-
Acknowledgement cell transplantation as first-line therapy in peripheral T-cell
The study was supported in part by AIRC. lymphomas: results of a prospective multicenter study.
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